LASIK News and Information. Hard-Hitting Reporting on the LASIK Industry.

Thirty-one months after it back-burnered a former CDRH [FDA’s Center for Devices and Radiological Health] branch chief’s petition seeking withdrawal of the LASIK indication for ophthalmic lasers based on unacceptably high permanent injury rates, CDRH has been sent a new retrospective study indicating that 21% of patients with serious corneal pain had received laser surgery on their eyes. The 6/14 study, from Harvard Medical School assistant clinical professor and Boston EyePain Foundation founder Perry Rosenthal, found 21 out of 100 consecutive patients diagnosed with centralized corneal pain had previously undergone laser keratorefractive surgery.

In his moribund petition, former CDRH branch chief for diagnostic and surgical devices Morris Waxler complained about a LASIK industry-promoted injury rate of less than 1% on which his review team had based its approval of the devices, compared with his subsequent assessment of an injury rate in excess of 20%. Waxler alleged that “Manufacturers and their collaborators withheld more than 10% of the adverse event data from 13 of the 25 studies, more than 20% from 12 studies, and more than 40% from seven studies.”

He said manufacturers pressured FDA to not include halos, glare, night vision problems, and dry eyes as adverse events in order for their lasers to meet FDA’s requirement of a less-than-1% adverse event rate. After approval, FDA decided these “symptoms” should be reportable events.

The new study by Rosenthal, which was rejected by two ophthalmic professional journals* heavily supported by the LASIK industry, carries the adverse event rate far beyond the six-month post-operative followup point in most of Waxler’s data, extending out as far as 15 years post-op. Rosenthal found eight patients who had experienced symptoms immediately after surgery, three whose symptoms were delayed between three and 28 days, two who experience symptoms between one and six weeks post-op, and eight whose symptoms began between one and 15 years post-op.

Rosenthal’s study describes the symptoms observed as chronic centralized neuropathic corneal pain. It says the recognition that this “can be a complication of laser keratorefractive surgery is the first step to developing mechanism-based treatments for this overlooked, crippling and currently intractable neurological complication.”

Rosenthal acknowledges in the study that the 21 subjects described differed from those who experienced “typical” post-LASIK dry eye-like pain in that they reported “higher intensity descriptors such as burning, aching, pressure, stabbing and in many of these patients, the presence of otherwise unexplainable photosensitivity (photoallodnia).”

He dismisses what he calls “anecdotal observations” that suggest centralized corneal neuropathic pain is rare. “This begs the question of why some people are susceptible to this complication,” he writes. “Vulnerability to neuropathic pain is believed to be influenced by certain genetic and epigenetic factors and efforts to develop useful predictive tests continue, including measurements of an individual’s endogenous sensitivity to pain.”

Rosenthal recommends screening of LASIK candidates for family history of autoimmune diseases which are known to be associated with a higher incidence of peripheral neuropathies. “Reports that delayed treatment of post-operative pain has a deleterious effect on pain outcomes suggest that [post LASIK] pain should be treated aggressively and perhaps even preemptively,” Rosenthal says in his study report. “In this context, early interventions that accelerate corneal epithelial and nerve healing and suppress inflammation may also be helpful in avoiding the transition to centralized corneal neuropathic pain. Because of the devastating nature of this complication the search for effective topical analgesics capable of being used safely prior to and for an extended period of time after surgery is, in my opinion, a high priority.”

* Elsevier’s [Ophthalmology:] Journal of the American Academy of Ophthalmology and The Journal of Cataract and Refractive Surgery

LNW: Good evening, Justice, and thanks for giving us this interview. Tell us about yourself. How did you become interested in LASIK?

Justice: I had a bad outcome from LASIK several years ago. I suffer from chronic dry eyes and distorted night vision — starbursts, halos, double vision… It turned my life upside down. I needed to understand why, what went wrong, and if it could be corrected. So that’s why I began my research.

LNW: And what did you find out? I mean, what went wrong?

Justice: Well, nothing went wrong according to my surgeon. But really, everything went wrong. When you do surgery on perfectly healthy, normal tissue… When you create a flap one-third the thickness of the cornea, and then vaporise more of the cornea with a laser, the cornea never recovers fully. Researchers have found permanent pathologic changes in all post-LASIK corneas studied.

LNW: You said you have night vision problems. Do you have large pupils?

Justice: Yes, and of course, that’s the problem.

LNW: Where did your research lead, as far as finding a solution for your vision problems?

Justice: Well, I consulted several leading surgeons. They proposed a retreatment. One surgeon actually suggested corneal transplant, bilateral. By that point I knew the risks associated with another surgery. Not only that, but also, the data seemed unconvincing that a retreatment would be effective. I decided to try rigid contact lenses, but my expectations were low because I had not been able to tolerate hard lenses before LASIK, and now, with my eyes much drier after LASIK, I knew they would be difficult to tolerate, and that was the case.

LNW: How has LASIK-induced dry eyes affected you?

Justice: I’m glad you asked that question because, unless you’ve experienced first-hand the pain and burning and all the rest that goes with it, people seem to think that dry eyes is just a minor issue that is easily managed with eye drops. But that’s definitely not the case. It has a huge impact on my life. I have to plan my activities around it. I always carry eye drops and goggles wherever I go. My eyelids stick to my eyes. It’s scary and painful. I instill eyedrops several times throughout the night. My optometrist once told me, “Your corneas are pretty beat up”. Beat up from the dryness and trying to wear lenses.

LNW: Let me get this straight. You need to wear hard lenses because your vision is impaired by LASIK, but LASIK caused you to have extremely dry eyes which makes it difficult, or impossible, to tolerate lenses?

Justice: (laughs) Yeah, crazy, right?

LNW: And tell our readers how LASIK causes dry eyes.

Justice: Mainly because corneal nerves are damaged. A normal cornea is highly innervated. It needs to be to protect your eyes, to let you know if your eyes are dry, to blink, or if you get sand in your eyes, to make tears to wash the sand out. But LASIK cuts the nerves and destroys nerves in the cornea. The feed-back loop is disrupted. The eyes are dry but there’s no information transmitted from the corneal surface telling the brain to send the message back to the lacrimal glands to produce tears.

LNW: What did your LASIK surgeon tell you, or warn you, about dry eyes before LASIK?

Justice: He never mentioned it. I still have a glossy brochure from his office which said that you’ll need to use eye drops for two weeks after LASIK.

LNW: Just two weeks?

Justice: That’s what it says. Two weeks.

LNW: The FDA website warns that dry eyes after LASIK can be permanent, so…

Justice: Right, I was not informed. You think you can trust doctors. It’s just not in our DNA to believe a doctor would hurt you.

LNW: I’m sorry. Is there anything else you would like to say about your experience?

Justice: Well, it’s not just the dry eyes and the bad night vision. It’s the betrayal of trust and the denial. It’s a bitter pill to swallow. It takes its toll. And then the cost. It’s crazy what you spend trying to manage LASIK complications. Thousands of dollars, year after year. And the ripple effect on all aspects of your life, and even your family’s lives. It’s devastating. And you feel as if you have no future. It’s not the life you expected. But you learn to keep going, you have to.

LNW: You’re wearing glasses. What is your vision like with glasses?

Justice: Yes, I started regressing right away, and my vision has been unstable ever since. In the daylight with glasses I see pretty well. I can function normally in bright light. But in dim light, or night-time, forget it. I dread the short days of winter. I don’t drive at night. I also have induced floaters, which bother me in bright light, I almost forgot. (laughs).

LNW: Floaters, dry eyes, bad night vision, regression? Anything else?

Justice: Induced astigmatism. And DLK.

LNW: Tell our readers. What is DLK?

Justice: Diffuse lamellar keratitis. Inflammation of the cornea. I had it in one eye and it left mild scarring.

LNW: Do you believe you were a bad candidate?

Justice: Yes, I do. I was becoming intolerant to my soft contact lenses, which indicates dry eyes, so that should be a contraindication. And I have large pupils, and that’s a definite contraindication, regardless what you might hear, it is a contraindication, period. But even if you’re a so-called ‘perfect candidate’, LASIK always leads to dry eyes, at least for a period of time, and virtually always reduces night vision. It’s a matter of severity. If your eyes are dry before, they’re going to be a lot drier. If you have large pupils, you’re going to have worse night vision than someone who has smaller pupils with the same refractive error. I see LASIK ads talking about newer technology and better night vision. No technology can treat a patient, appropriately, with very large pupils without taking off too much tissue. You only have so much cornea.

LNW: Yeah, if you remove too much corneal tissue, you place the patient at risk of corneal ectasia.

Justice: Right. That’s the complication that LASIK surgeons most want to keep quiet.

LNW: Justice, thanks for telling us your story. Before we wrap this up, let’s talk about LasikScandal.com. It’s a great looking site.

Justice: Thanks, but I’m not the web designer. Jeff and Bob deserve the credit.

LNW: You write content for the site?

Justice: I wrote some of the content, yes.

LNW: Well, it’s very compelling, well researched. I understand you’re building a patient registry.

Justice: Yes, now that we’ve got a site up, we’re going to be focusing on the patient registry and the forum.

The U.S. Food and Drug Administration today warned five eye care providers to stop the misleading advertising and promotion of refractive lasers used in eye surgery procedures such as LASIK. The FDA found that the providers’ advertisements and promotional materials did not offer consumers adequate information about associated risks, as well as warnings and possible adverse events.

The five providers that received FDA Warning Letters are:

20/20 Institute Indianapolis LASIK, of Indianapolis

Scott Hyver Visioncare Inc., of Daly City, Calif.

Rand Eye Institute, of Deerfield Beach, Fla.

Eye Center of Texas, of Bellaire, Texas

Woolfson Eye Institute, of Atlanta

“Advertising by many eye care professionals who perform laser vision correction surgery provides patients with the risk information that they need to make informed decisions,” said Steve Silverman, compliance director at FDA’s Center for Devices and Radiological Health. “But providers whose advertising does not provide adequate risk information are finding out today that the FDA is serious about consumer protection.”

The U.S. Food and Drug Administration today warned five eye care providers to stop the misleading advertising and promotion of refractive lasers used in eye surgery procedures such as LASIK. The FDA found that the providers’ advertisements and promotional materials did not offer consumers adequate information about associated risks, as well as warnings and possible adverse events.

The five providers that received FDA Warning Letters are:

20/20 Institute Indianapolis LASIK, of Indianapolis

Scott Hyver Visioncare Inc., of Daly City, Calif.

Rand Eye Institute, of Deerfield Beach, Fla.

Eye Center of Texas, of Bellaire, Texas

Woolfson Eye Institute, of Atlanta

“Advertising by many eye care professionals who perform laser vision correction surgery provides patients with the risk information that they need to make informed decisions,” said Steve Silverman, compliance director at FDA’s Center for Devices and Radiological Health. “But providers whose advertising does not provide adequate risk information are finding out today that the FDA is serious about consumer protection.”

The U.S. Food and Drug Administration today warned five eye care providers to stop the misleading advertising and promotion of refractive lasers used in eye surgery procedures such as LASIK. The FDA found that the providers’ advertisements and promotional materials did not offer consumers adequate information about associated risks, as well as warnings and possible adverse events.

The five providers that received FDA Warning Letters are:

20/20 Institute Indianapolis LASIK, of Indianapolis

Scott Hyver Visioncare Inc., of Daly City, Calif.

Rand Eye Institute, of Deerfield Beach, Fla.

Eye Center of Texas, of Bellaire, Texas

Woolfson Eye Institute, of Atlanta

“Advertising by many eye care professionals who perform laser vision correction surgery provides patients with the risk information that they need to make informed decisions,” said Steve Silverman, compliance director at FDA’s Center for Devices and Radiological Health. “But providers whose advertising does not provide adequate risk information are finding out today that the FDA is serious about consumer protection.”

The U.S. Food and Drug Administration today warned five eye care providers to stop the misleading advertising and promotion of refractive lasers used in eye surgery procedures such as LASIK. The FDA found that the providers’ advertisements and promotional materials did not offer consumers adequate information about associated risks, as well as warnings and possible adverse events.

The five providers that received FDA Warning Letters are:

20/20 Institute Indianapolis LASIK, of Indianapolis

Scott Hyver Visioncare Inc., of Daly City, Calif.

Rand Eye Institute, of Deerfield Beach, Fla.

Eye Center of Texas, of Bellaire, Texas

Woolfson Eye Institute, of Atlanta

“Advertising by many eye care professionals who perform laser vision correction surgery provides patients with the risk information that they need to make informed decisions,” said Steve Silverman, compliance director at FDA’s Center for Devices and Radiological Health. “But providers whose advertising does not provide adequate risk information are finding out today that the FDA is serious about consumer protection.”

The U.S. Food and Drug Administration today warned five eye care providers to stop the misleading advertising and promotion of refractive lasers used in eye surgery procedures such as LASIK. The FDA found that the providers’ advertisements and promotional materials did not offer consumers adequate information about associated risks, as well as warnings and possible adverse events.

CDRH director Jeff Shuren was told 7/24 he has a “moral, if not a legal, obligation to follow up directly” with a patient who told his Center in a 6/6 MedWatch report that “I intend to end my life soon” because of LASIK-related eye injury. The plea came in an email to Shuren from LASIK victim/activist and CDRH advisory committee consumer representative Paula Cofer. Her email comes as Shuren was presumably hoping the LASIK controversy ─ a technology “too dangerous to be allowed” ─ had been left on the way, way backburner.

Cofer wrote:

“I urgently wish to bring your attention to a MedWatch report which was received by the FDA on June 6, 2012. This report was submitted voluntarily by an injured LASIK patient who expressly states his or her intention to commit suicide:

‘I have chronic aqueous deficient dry eye a/k/a neurotrophic keratopathy or refractory dry eye. My eyes do not tear when they are dry or come into contact with irritants and allergens. This is an extremely painful and degenerative condition though I don’t think I will be around to see exactly how bad it gets because I intend to end my life soon. My doctor claims that it is not possible for this to be a result of LASIK. However, when pressed he said that up to 40% of LASIK patients have some degree of residual dry eye. He is full of contradictions. It depends what you’re asking him and in what context. The answer changes regularly. It took me 6 years to find a doctor that finally told me that this condition is in fact due to LASIK surgery. This is due to a concerted effort by ophthalmologists to cover up for each other. Even though they knew better they sent me on a 6 year quest to find out what I should have been told before the surgery. LASIK causes extreme dry eyes in many people, especially people like me with high risk factors.’

“I happened upon this report,” Cofer tells Shuren, “as I was reviewing the most recent LASIK MedWatch reports contained in the Maude database, which is something that I do routinely in my continuing efforts to raise awareness of the risks of LASIK surgery.

“I am aware of five LASIK-related suicides and believe that this patient is in imminent danger.

“I believe the FDA has a moral, if not a legal, obligation to follow up directly with this patient. Please reply by e-mail within 3 days to advise that you are taking appropriate steps.”

During an inspection of your firm located in Atlanta, Georgia, on October 5-6, 2011, an investigator from the United States Food and Drug Administration (FDA) determined that your firm is a medical device user facility that is subject to the statutory requirements of the Medical Device Reporting (MDR) regulation, found at Title 21 Code of Federal Regulations (CFR) Part 803.

The ophthalmic laser used at your facility to perform Laser-Assisted In Situ Keratomileusis (LASIK) procedures is a medical device under section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. § 321(h), because it is intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment or prevention of disease, or to affect the structure or function of the body.

Our inspection revealed that your facility’s device is misbranded under section 502(t)(2) of the Act, 21 U.S.C. 352(t)(2), in that your firm failed or refused to furnish material or information respecting the device that is required by or under section 519 of the Act, 21 U.S.C. § 360i, and 21 CFR Part 803 – Medical Device Reporting. Significant violations include, but are not limited to, the following:

Failure to submit a FDA Form 3500A or an electronic equivalent to the device manufacturer within ten working days of becoming aware of information that reasonably suggests that a device has or may have caused or contributed to a serious injury to a patient of your facility, as required by 21 CFR 803.30(a)(2). For example, the Customer Incident and Event Reporting Form dated April 21, 2011, for (b)(6), indicated that an EDIR surgery was conducted to remove debris from a patient without detailing the reason for the procedure and the facility’s rationale for considering the event to be not reportable.

The information included for (b)(6) suggests that, after the LASIK procedure, the patient lost more than 2 lines of best corrected visual acuity (BCVA). FDA believes that the loss of 2 lines of BCVA represents an impairment of vision function. Therefore, the information included for (b)(6) meets the definition of a serious injury found at 21 CFR 803.3, which should have been reported by your facility to the device manufacturer. There is no evidence that the complaint was forwarded to the manufacturer.

We reviewed your facility’s response and conclude that it is not adequate. The response states that your facility does not consider adverse events as reportable when the event is not the result of laser equipment, but rather the patient’s response to post-operative care. Your facility should be aware that 21 CFR 803.3 states that, if a medical device may have been a factor in a serious injury, then such event meets the criteria for reportability.

Your firm should take prompt action to correct the violations addressed in this letter. Failure to promptly correct these violations may result in regulatory action being initiated by the FDA without further notice. These actions include, but are not limited to, seizure, injunction, and civil money penalties. Also, federal agencies may be advised of the issuance of Warning Letters about devices so that they may take this information into account when considering the award of contracts.

Please notify this office in writing within fifteen business days from the date you receive this letter of the specific steps your firm has taken to correct the noted violations, as well as an explanation of how your firm plans to prevent these violations, or similar violations, from occurring again. Include documentation of the corrections and/or corrective actions (including any systemic corrective actions) that your firm has taken. If your firm’s planned corrections and/or corrective actions will occur over time, please include a timetable for implementation of those activities. If corrections and/or corrective actions cannot be completed within fifteen business days, state the reason for the delay and the time within which these activities will be completed. Your firm’s response should be comprehensive and address all violations included in this Warning Letter.

Your firm’s response should be sent to: Food and Drug Administration, Center for Devices and Radiological Health, Office of Surveillance and Biometrics, MDR Policy Branch, White Oak Building 66, 10903 New Hampshire Avenue, Room 3208, Silver Spring, MD 20993. Refer to the Unique Identification Number #255515 when replying. If you have any questions about the contents of this letter or wish to discuss MDR reportability criteria or schedule further communications, please contact: MDR Policy Branch at (301) 796-6670 or by email at MDRPolicy@fda.hhs.gov.

If your facility wishes to submit MDR reports via electronic submission, it can follow the directions stated at the following URL: http://www.fda.gov/MedicalDevices/deviceregulationandguidance/guidancedocuments/ucm094529.htm#where1

Finally, you should know that this letter is not intended to be an all-inclusive list of the violations at your firm’s facility. It is your firm’s responsibility to ensure compliance with applicable laws and regulations administered by FDA. The specific violations noted in this letter and in the Inspectional Observations, FDA 483, issued at the close of the inspection may be symptomatic of serious problems in your firm. Your firm should investigate and determine the causes of the violations, and take prompt actions to correct the violations and bring the products into compliance.

David Muller, who as founder and CEO of Summit Technology gained in 1996 the first excimer laser approval for the controversial LASIK vision correction surgical procedure, announced 3/8 the submission of an NDA for VibeX (riboflavin ophthalmic solution)/KXL System to be used in treating corneal damage often associated with LASIK. The announcement came from his new company Waltham, MA-based Avedro Inc., which Muller formed with venture capital backing in 2007 after Summit was acquired by Alcon.

The new NDA seeks an indication for the treatment of keratoconus (a naturally occurring disease in which the cornea distends in a cone shape) and corneal ectasia following refractive surgery (LASIK). Morris Waxler, the CDRH branch chief who led the approval of Muller’s device in 1996 and others like it, is now aggressively seeking the removal of their LASIK indication based on a higher permanent injury rate from the LASIK procedure than disclosed by the sponsors in their data submissions.

Avedro’s news release quoted Cornea and Laser Eye Institute medical monitor and director Peter Hersh as saying that the “ophthalmology community is now looking forward to the possibility of offering cross-linking to keratoconus and corneal ectasia patients in the near future, addressing a significant unmet medical need. Currently, there are limited treatment options for decreasing the natural progression of keratoconus and ectasia. Cross-linking has the promise of stabilizing these progressive corneal disorders and maintaining patients’ visual function over time.”

Corneal collagen cross-linking with riboflavin and ultraviolet light is described by the National Keratoconus Foundation as a process that increases natural collagen crosslinks in the cornea, thus strengthening it and preventing it from further bulging out. The treatment’s possible extension to treat post-LASIK ectasia was recognized by FDA last year as deserving of orphan drug designation, offering seven years market exclusivity. Avedro’s news release said the VibeX/KXL System for corneal collagen cross-linking received the European CE Mark in 2010 and has been commercially available internationally since then.